Abstract : Ascites 13762 cells, a highly metastatic and malignant rat mammary adenocarcinoma cell line, express a cell surface glycoprotein called ASGP2 that possesses two domains believed to interact with and stimulate growth factor receptors of the ErbB family. These cells also express p1 85erbB2/neu, a member of the ErbB family whose aberrant activation probably plays a role in tumorigenesis and tumor progression in a significant subset of breast cancer patients. ASGP2 and p185erbB2/neu exist in a complex at the surface of the ascites 13762 cells, raising the possibility that these cells stimulate their own growth or malignancy through an autocrine mechanism involving the ASGP2/p185erbB2/neu interaction. The overall goal of the studies outlined in this proposal is to test this hypothesis. Studies are aimed at examining the effect of ASPG2/p185erbB2/neu complex expression on the growth and transformation of cultured mammalian cells, including human breast cancer cells. We have attempted to stably express ASGP2 in a variety of cell lines and have found only one, the human mammary tumor cell line MCF7, that is capable of supporting the stable expression of this protein. Studies are currently underway to characterize the growth properties of transfectants.